Suppressive effect of nantenine, isolated from Nandina domestica Thunberg. on the 5-hydroxy-L-tryptophan plus clorgyline-induced head-twitch response in mice

Abstract

We investigated the effects of nantenine (9,10-Methylenedioxy-1, 2 dimethoxyaporphine), a major alkaloid isolated from the fruit of Nandina domestica Thunb (Berberidaceae), on the 5-HT 2A receptor-mediated head-twitch response (HTR) in mice. Intraperitoneal (i.p.) injection of nantenine (13.3, 20 and 30 mg/kg) as well as the 5-HT 2A receptor antagonist ketanserin (0.0625, 0.25 and 1 mg/kg) inhibited the 5-hydroxy-L-tryptophan ( l-5-HTP; 75 mg/kg, i.p.) plus monoamine oxidase inhibitor, clorgyline (1 mg/kg, i.p.)-induced HTR in a dose-dependent manner. In contrast, neither l-5-HTP plus clorgyline nor 5-HT 1A agonist, 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT; 5 μg/mouse, i.c.v.)-induced head weaving was affected by nantenine or ketanserin. Furthermore, neither nantenine (up to 30 mg/kg) nor ketanserin (up to 1 mg/kg) affect on the locomotor activity. In the receptor binding studies, nantenine showed affinity to the 5-HT 2A receptors ( K i = 0.4 μM), while it had less affinity toward α 1-adrenergic ( K i = 2.1 μM) and D 2-dopaminergic ( K i = 1.7 μM) receptors of the mouse brain. These results suggest that nantenine inhibits l-5-HTP plus clorgyline-induced head-twitch response by blocking 5-HT 2A receptors in the central nervous system.